JPH0417195B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing 7-deazapurine derivatives and salts thereof. Among the 7-deazapurine derivatives that can be produced by the method of the present invention, supermodified bases (e.g., Q base,
PfeQ ₁ , base) is linked to a specific tRNA (tRNA ^Tyr ,
It is widely distributed in nature as the first component of the anticodon of tRNA ^His , tRNA ^Asp , and tRNA ^Asn , and is thought to play an important role in protein synthesis by recognizing genetic information from mRNA. There is. On the other hand, with the recent development of basic biochemical research on tRNA, it has been discovered that in cancer cells, the incorporation of Q base into the tRNA precursor is not complete, and that Q-deficient tRNAs universally exist, and that Q base is supplied from the outside. It has become clear that Q-deficient tRNA returns to normal tRNA as a result of this, and that this uptake phenomenon by cancer cells is also observed for specific 7-deazapurine derivatives [Satoshi Nishimura, Metabolism, vol. 17, extra. Special issue “Cancer ’80” p.127-136
(1980)]. Recently, the chemical synthesis of Q bases has been reported by Goto et al. [N. Okada et al, Journal of
Biological Chemistry, 254 , 3067 (1979)]
It requires a long process and a special reaction, and is not industrially satisfactory at all. Therefore, in order to establish an advantageous method for industrial production of 7-deazapurine derivatives, the present inventors
After conducting various studies, it was discovered that the desired product could be advantageously obtained by carrying out a substitution reaction at the 7-position of the derivative, and as a result of further research based on this, the present invention was completed. The present invention provides (1) general formula [In the formula, R ₁ represents a hydrogen atom, an alkanoyl group, or an aroyl group, R ₂ and R ₃ represent an alkyl group, an alkenyl group, or an aralkyl group with a methylene group at the α position, respectively, and R ₂ and R ₃ are adjacent to each other. may form a cyclic amino group together with the nitrogen atom. ] The 7-deazapurine derivative or its salt represented by the general formula [In the formula, R ₄ and R ₅ each represent a hydrogen atom or an alkyl group, an alkenyl group, a cycloalkyl group, a cycloalkenyl group, an aralkyl group, or an aryl group, each of which may have a substituent, and R ₄
and R ₅ may form a cyclic amino group together with the adjacent nitrogen atom. however,

【formula】 The base is

[Formula] is not the same as the group. A general formula characterized by being subjected to a substitution reaction with an amine represented by or a salt thereof [In the formula, X, R ₁ , R ₄ and R ₅ have the same meanings as above. ] This is a method for producing a 7-deazapurine derivative or a salt thereof. In the above formula, the alkanoyl group represented by R ₁ preferably has 1 to 18 carbon atoms, and examples thereof include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl,
Examples include octanoyl, 2-ethylhexanoyl, nonanoyl, decanoyl, undecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, and among others, carbon atoms 1 to 10
are conveniently used. The aroyl group preferably has 7 to 12 carbon atoms, and examples thereof include benzoyl, toluoyl, naphthoyl, etc. Among them, benzoyl group is preferably used. The groups represented by R ₂ and R ₃ may be the same or different, and the alkyl group in which α is a methylene group has about 1 to 10 carbon atoms, such as methyl, ethyl, n-propyl, n- Examples include butyl, isobutyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl groups, among which alkyl groups having about 1 to 6 carbon atoms are conveniently used. The alkenyl group having a methylene group at the α-position has 3 to 3 carbon atoms.
13 or so, such as allyl (2-propenyl),
Examples include 2-butenyl, 2-pentenyl, 2-hexenyl, 4-propyl-2-pentenyl, cinnamyl, 2-nonyl-2-butenyl groups, among which alkenyl groups having about 3 to 9 carbon atoms are conveniently used. It will be done. These alkyl groups and alkenyl groups may have 1 to 3 substituents at any position other than the α-position, and examples of such substituents include alkyl groups having about 1 to 4 carbon atoms (e.g., methyl , ethyl, propyl, isopropyl, butyl,
isobutyl, sec-butyl, tert-butyl), alkoxy groups having about 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-
butoxy group), alkanoyl group having about 1 to 4 carbon atoms (e.g., formyl, acetyl, propionyl, n
-butyryl, iso-butyryl), hydroxyl, nitro, halogen (e.g., fluorine, chlorine, bromine, iodine), carboxy, cyano, trifluoromethyl, dialkylamino (e.g., dimethylamino, diethylamino) , dipropylamino, diisopropylamino, dibutylamino groups), alkanoylamide groups (e.g. formamide, acetamide,
Propionylamide, butyrylamide, isobutyrylamide groups), etc. As the aralkyl group in which the α-position represented by R ₂ and R ₃ is a methylene group, for example, the number of carbon atoms is 7 to 12.
Examples include benzyl, phenethyl, 3-phenylpropyl, naphthylmethyl, and naphthylethyl groups, among which benzyl group is advantageously used. These aralkyl groups also have alkylene chain moieties other than the α-position and/or aryl (phenyl)
The ring portion may have a substituent, and such substituents include the groups exemplified above for the alkyl group and alkenyl group. Examples of the cyclic amino group formed by R ₂ and R ₃ together with the adjacent nitrogen atom include a 5- to 6-membered cyclic amino group, in which a second ring heteroatom (e.g., N , O). Examples of such cyclic amino groups include 1-pyrrolidinyl, 1-pyrrolinyl, 1-imidazolidinyl, 1-imidazolinyl, 1-pyrazolidinyl, 1-pyrazolinyl, morpholino, piperidino, and 1-piperazinyl groups, and these cyclic amino groups may have a substituent except for the position adjacent to the nitrogen atom (α-position), and examples of such substituents include the groups exemplified for the alkyl group and alkenyl group. In the above formula, the alkyl group represented by R ₄ and R ₅ is, for example, an alkyl group having 1 to 18 carbon atoms (e.g., methyl, ethyl, propyl, isopropyl,
Butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl,
undenyl, dodecyl, tetradecyl, hexadecyl, octadecyl, 1,2-dimethylpropyl, 1-ethylpropyl, 1,2,2-trimethylpropyl, 1-propylbutyl, 2-ethylhexyl groups). The alkenyl group represented by R ₄ and R ₅ has, for example, a carbon number of 1 to 12
Alkenyl groups [e.g., vinyl, allyl,
1-methylvinyl, 2-methylvinyl, 1-octenyl, 1-decenyl group]. Examples of the cycloalkyl group include cycloalkyl groups having 3 to 12 carbon atoms (eg, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl group). Examples of the cycloalkenyl group represented by R ₄ and R ₅ include cycloalkenyl groups having 3 to 8 carbon atoms (e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl). , cyclooctadienyl group). Examples of the aralkyl group represented by R ₄ and R ₅ include aralkyl groups having 7 to 13 carbon atoms (eg, benzyl, α-methylbenzyl, phenethyl, and diphenylmethyl groups). The aryl group represented by R ₄ and R ₅ is, for example, an aryl group having about 6 to 10 carbon atoms (e.g., phenyl, α-naphthyl, β-naphthyl group)
can be given. R ₄ and R ₅ may form a ring together with adjacent nitrogen atoms. Such a ring is preferably a 4- to 10-membered ring, such as azetidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolinyl, piperidino, morpholino, dihydropyridyl, tetrahydropyridyl, N-methylpiperazinyl, N-ethylpipe. Radinyl, azacycloheptyl, azacyclooctyl, isoindole, indole, indolinyl, isoindolinyl, azacyclononyl, azacyclodecyl, and the like. The alkyl group, alkenyl group, cycloalkyl group, cycloalkenyl group, aralkyl group or aryl group represented by these R ₄ and R ₅ or
The ring formed by R ₄ and R ₅ together with adjacent nitrogen atoms may have 1 to 3 substituents. Such substituents include, for example, alkyl groups having about 1 to 4 carbon atoms (e.g., methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-
butyl), an alkoxy group having about 1 to 4 carbon atoms that may have a hydroxyl group as a substituent (e.g., methoxy, exy, propoxy, iso-propoxy, n
-butoxy, iso-butoxy, sec-butoxy,
tert-butoxy group), alkanoyl group having about 1 to 4 carbon atoms (e.g. formyl, acetyl, propionyl, n-butyryl, iso-butyryl group), carbon number 1
-4 or so alkanoyloxy groups (e.g., formyloxy, acetyloxy, propionyloxy,
n-butyryloxy, iso-butyryloxy group),
Carboxy group, alkoxycarbonyl group having about 2 to 4 carbon atoms (e.g., methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, iso-
propoxycarbonyl group), halogen atom (e.g.
fluorine, chlorine, bromine, iodine), hydroxyl group, nitro group,
Cyano group, trifluoromethyl group, amino group, monoalkylamino group (e.g. methylamino, ethylamino, propylamino, isopropylamino,
butylamino group), dialkylamino group (e.g. dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino group),
Examples include alkanoylamide groups (eg, formamide, acetamide, propionylamide, butyrylamide, isobutyrylamide groups). In addition, in general formulas () and ()

[Formula] The group is a compound represented by the general formula () in things

[Formula] shall not be the same as the group. In the substitution reaction of the present invention, for example, the compound () or its salt and the compound () or its salt are mixed at a molar ratio of about ()/() = 1 to 20 (molar ratio) using the compounds themselves or an appropriate reaction solvent to approx. This can be carried out by carrying out a moderate reaction at a reaction temperature ranging from 0°C to the boiling point of the reaction solvent, preferably from about 20 to 100°C, for about 1 hour to 5 days. Furthermore, when compound () is converted into a quaternary salt such as methyl bromide, methyl iodide, methanesulfonic acid methyl ester, benzenesulfonic acid methyl ester, p-toluenesulfonic acid methyl ester, etc., the reaction conditions are even milder. You can also proceed. At this time, the resulting quaternary salt of compound () may be isolated or may be directly subjected to a substitution reaction with compound () without isolation. In addition, if R ₁ is an alkanoyl group or an aroyl group, if necessary, the reaction solution can be used as it is for about 70 minutes.
Continuing to heat at ~100°C to carry out the dealkanoylation or dealoylation reaction of _R1 , or hydrolysis (e.g., acid hydrolysis, alkaline hydrolysis, ammonialysis) by a method known per se. Dealalkanoylation or dealoylation can be carried out by. compound() and compound()
Examples of reaction solvents in the substitution reaction include water, methanol, ethanol, propanol,
Butanol, pentanol, tetrahydrofuran, dioxane, acetonitrile, pyridine, dimethylformamide, dimethyl sulfoxide, sulfolane or an appropriate mixed solvent thereof is used. When compound () or compound () is used in the form of a salt, a base (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, triethylamine, N-methylmorpholine) or a salt (e.g. , sodium chloride, potassium chloride, calcium chloride, sodium carbonate, potassium carbonate, sodium hydrogen carbonate) at optimum pH (usually,
By adjusting the pH to about 5 to 13), the desired product () can be advantageously produced. Alkyl group, alkenyl group represented by R ₄ and R ₅ ,
Among these substituents of a cycloalkyl group, cycloalkenyl group, aralkyl group or aryl group, for example, in the case of a carboxy group, hydroxyl group, amino group or alkylamino group, if necessary, a method known per se [ JFW McOmie,
Protective Groups in Organic Chemistry
Plenum Press, London and New York
(1973)] or already protected substituents (e.g., alkanoyloxy group, alkoxycarbonyl group, alkanoylamide group)
Using a raw material compound () having the above, a substitution reaction may be performed with another raw material compound () to form a compound (), and then a protecting group elimination reaction may be performed. The protective group elimination reaction is carried out by subjecting the protective group to a commonly used protective group elimination reaction. For example, acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid,
trifluoroacetic acid, boron trifluoride, boron tribromide, hydrogen bromide-acetic acid) or bases (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide, potassium carbonate, sodium carbonate,
Ammonia water, methylamine, dimethylamine,
ethylamine, diethylamine, trimethylamine, triethylamine) and a suitable solvent (e.g., water, methanol, ethanol, propanol, butanol, dioxane, tetrahydrofuran, methyl ether, ethyl ether, dichloromethane, chloroform, carbon tetrachloride, benzene,
(toluene, xylene or an appropriate mixed solvent thereof) at about -50 to 100°C, preferably -10 to 50°C
at a temperature of about 30 minutes to 100 hours, preferably about 1
Either react for ~20 hours or add a suitable catalytic reduction catalyst (e.g., palladium, platinum, rhodium, ruthenium, nickel) and react in a suitable solvent (e.g., water, methanol, ethanol, propanol, butanol, dioxane). , tetrahydrofuran, methyl ether, ethyl ether, benzene, toluene, xylene, ethyl acetate, methyl acetate, acetic acid or an appropriate mixed solvent thereof), about
This is carried out by catalytic reduction at a temperature of 10 to 50°C for about 1 to 100 hours. The 7-deazapurine derivative () produced by the method of the present invention can be isolated from the reaction mixture by conventional separation and purification means, such as concentration, solvent extraction, chromatography, recrystallization, etc. Furthermore, when compound () is obtained in free form, it may be converted into a pharmaceutically acceptable salt form by a conventional method. Examples of salts of the compound () include mineral acid salts with hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid, etc., oxalic acid, tartaric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid. , organic acid salts with camphorsulfonic acid, etc., and quaternary salts with methyl bromide, methyl iodide, methanesulfonic acid methyl ester, benzenesulfonic acid methyl ester, p-toluenesulfonic acid ester, etc. When the compound () is obtained in the form of a salt other than a quaternary salt, it can also be made into a free form if desired. In this case, it can be easily carried out by subjecting the salt of the compound () to a commonly used method such as neutralization reaction or anion exchange chromatography. The compound () or its salt obtained in this way can be used to improve the growth of L5178Y cultured cells in vitro and Meth A, Sarcoma180 in vivo.
It has an antitumor effect because it suppresses the proliferation of each of these. In addition, the compound () or its salt is
Even if a dose of 200 mg/Kg was administered intraperitoneally to mice,
No deaths were observed. Therefore, the compound () or a salt thereof may be used in warm-blooded animals, especially mammals, e.g.
It can be used as an antitumor agent for the purpose of treating tumors in mice, rats, cats, dogs, rabbits, etc. When used as an antitumor agent, it can be prepared as such or in the form of powders, granules, preparations, capsules, suppositories, etc. using pharmacologically acceptable carriers, excipients, diluents, etc., using commonly used methods. , can be administered orally or parenterally in the form of injections and the like. The dosage varies depending on the target animal, disease, symptoms, type of compound, administration route, etc., but in the case of oral administration, approximately 10 to 200 doses of the compound () are administered per day.
mg/Kg body weight, and in the case of parenteral administration, about 10-100 mg/Kg body weight per day. Furthermore, the compound () or its salt has antiviral and antibacterial effects against various viruses and microorganisms, and has low toxicity as mentioned above, so it is effective against warm-blooded animals, especially mammals (e.g., mice, rats, cats, etc.). It can be used as an antiviral agent, antibacterial agent, and disinfectant for the prevention and treatment of viral and bacterial infections in dogs, rabbits, and humans. When using the compound () or its salt as a bactericidal agent or disinfectant, for example, the compound () or its salt may be added to water, an isotonic glucose solution, an aqueous solution such as Ringer's solution, or a solution of about 0.5 to 500 mg/ml. The solution is made into a non-aqueous solution such as vegetable (e.g., cotton seed, peanut, corn, sesame) fatty oil and applied to the hands, feet, ears, etc. of a mammal to sterilize the administration site. It can be used for disinfection. You can also add the compound () or its salt to about 0.5 to 500
mg can be used orally in the form of tablets containing excipients such as lactose, starch, and talc for the prevention and treatment of viral infections and bacterial infections in the mammal. The dosage in this case is approximately 10 to 100% per day as the compound ()
The amount is 200mg/Kg body weight. The compound () used as a raw material in the method of the present invention can be produced, for example, by the reaction steps shown below. (In the above formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) In step A, the compound () and the general formula (In the formula, R ₂ and R ₃ have the same meanings as above.) Mannich reaction in the presence of formaldehydes)
[Organic Reactions 1 , 303 (1942);
Angewandte Chemie 68 , 265 (1956)]. Compound () and Compound () may be used in the form of salts, such as mineral acid salts with hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid, etc., carbonic acid, oxalic acid, tartaric acid, acetic acid, etc. , trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, and the like. Formaldehydes include reagents that have an equivalent effect to formaldehyde during the Mannich reaction, such as formaldehyde,
Examples include paraformaldehyde, formalin, methylal, ethylal, piperidinomethylphthalimide, and hexamethylenetetramine. In this Mannich reaction, compound () and compound () are ()/()=1 to 50
using themselves or a suitable reaction solvent in molar ratios at reaction temperatures ranging from about 0°C to the boiling point of the reaction solvent, preferably from about 20 to 100°C, for 10 minutes to 48°C.
After reacting for about a period of time, the desired compound (;X=O) can be obtained by treating with an acid. As the reaction solvent, water, methanol, ethanol, propanol, butanol, pentanol, tetrahydrofuran, dioxane, acetonitrile, pyridine, dimethylformamide, dimethylsulfoxide, sulfolane, or an appropriate mixture thereof is used. Adjust the pH of the reaction solution to an acid (e.g., hydrochloric acid, sulfuric acid, phosphoric acid, boric acid, acetic acid, oxalic acid, tartaric acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid), Bases (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, ammonia, triethylamine) or salts (e.g., sodium chloride, calcium chloride, sodium carbonate, potassium carbonate, sodium bicarbonate, ammonium chloride) The reaction rate and yield can be improved by adjusting the pH to an appropriate level (usually about 2 to 10). The acids used in the final acid treatment include, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid, acetic acid, oxalic acid, tartaric acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. can be given. The compound () produced by the above method can be isolated from the reaction mixture using conventional separation and purification means such as concentration, solvent extraction, recrystallization, chromatography, etc. as appropriate. When the compound () is obtained in free form in this manner, it may be converted into a salt form by a conventional method and used as a raw material compound in the method of the present invention. Examples of the salt of compound () include the same salts as the salts of compound () described above. The compound () used in the method of the present invention may be in the form of a salt. As the salt of compound (), the above-mentioned compound () and compound () can be used.
Salt and similar products can be mentioned. The method of the present invention can start from inexpensive and industrially easily available raw materials, has a short number of reaction steps, can obtain the desired product with a high reaction yield, is simple and easy to operate, and is advantageous in terms of equipment. Therefore, it is an industrially advantageous method for producing 7-deazapurine derivatives. The present invention will be explained in more detail with reference to Reference Examples and Examples below. In addition, in the reference example
The Rf value indicates a value determined by silica gel thin layer chromatography (manufactured by Merck & Co., Ltd., silica gel HPTLC). Reference example 1 2-n-octanoylaminopyrrolo[2,3-
d] Production of pyrimidin-4-one: 2-aminopyrrolo[2,3-d]pyrimidine-
4-one (6.0 g) was suspended in pyridine (80 ml),
While stirring on an ice bath, n-octanoyl chloride (22.8 g) was added. After heating the reaction mixture at 85°C for 30 minutes, the solvent was distilled off under reduced pressure, diluted hydrochloric acid was added to the residue, and the mixture was extracted with chloroform. The extracts were combined and concentrated to dryness, and the resulting residue was dissolved in 8% alcoholic ammonia (50 ml) and left at room temperature to precipitate the desired product (8.9 g) as crystals. NMR (DMSO−d ₆ /D ₂ O, 60MHz) δ 0.87
(1t, 3H), 1.30 (s, 10H), 2.47 (t, 2H), 6.47
(d, 1H), 6.80 (d, 1H). IR (KBr) ν 1640cm ^-1 Reference example 2 5-N,N-dibenzylaminomethyl-2-n
-Production of octanoylaminopyrrolo[2,3-d]pyrimidin-4-one: 2-n-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one obtained in Reference Example 1 (1.67 g ), dibenzylamine (3.6g) and 30%
Formalin (1.72 g) was dissolved and suspended in 80% aqueous acetic acid (60 ml), and after reaction at 60°C for 20 hours, the solvent and excess reagents were distilled off under reduced pressure. The resulting residue was dissolved in methanol (60 ml) and N-hydrochloric acid (60 ml), treated at 80°C for 1 hour, converted into an ammonia alkali, and concentrated to dryness. Water was added to the residue, extracted with chloroform, and the extracts were combined and evaporated to obtain a crude product. This product was recrystallized from diethyl ether to obtain the pure target product (2.43 g). NMR ( _CDCl3 / _D2O /DMSO- _d6 , 60MHz) δ
0.90 (1t, 3H), 1.30 (bs, 10H), 2.47 (t,
2H), 3.80 (s, 4H), 4.00 (s, 2H), 6.93 (s,
1H), 7.33 (bs, 10H). IR (KBr) ν 1645, 1615 cm ^-1 Rf = 0.17 (developing solvent, chloroform:methanol = 7:1). Reference Example 3 Production of 2-amino-5-N,N-dibenzylaminomethylpyrrolo[2,3-d]pyrimidin-4-one: 5-N,N-dibenzylaminomethyl obtained in Reference Example 2 -2-n-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (971 mg) was mixed with methanol/tetrahydrofuran (1:1,60
ml), 5N-KOH (2.5 ml) was added, and the mixture was stirred at room temperature for 60 hours. The solvent was distilled off under reduced pressure,
The resulting residue was purified by column chromatography using silica gel and ion exchange resin to obtain the desired product (601 mg). NMR ( _CDCl3 /DMSO- _d6 , 60MHz) δ 3.63
(s, 4H), 3.83 (s, 2H), 5.87 (bs, 2H), 6.60
(bs, 1H), 7.20 (m, 10H). IR (KBr) ν 1665, 1625, 1600 cm ^-1 Rf = 0.35 (developing solvent, chloroform:methanol = 4:1). Reference example 4 5-N,N-dimethylaminomethyl-2-n-
Production of octanoylaminopyrrolo[2,3-d]pyrimidin-4-one: In the same manner as in Reference Example 2, 2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and dimethylamine were combined. The desired object was obtained. Rf=0.13 (developing solvent, chloroform: 5.8%
NH ₃ /ethanol = 4:1) Reference example 5 (1) 2-amino-4-chloropyrrolo[2,3-
d] Production of pyrimidine: 2-aminopyrrolo[2,3-d]pyrimidin-4-one (45g) was dissolved in phosphorus oxychloride (150ml).
and stirred and reacted at 110°C for 3 hours. Excess phosphorus oxychloride was distilled off under reduced pressure, ice water (600 ml) was added to the residue to completely dissolve it, and the pH was adjusted to 9 with concentrated aqueous ammonia while cooling and stirring. The resulting precipitate was collected, washed with water, and then recrystallized from hot methanol (4) to obtain the desired product (34.6 g). NMR (DMSO-d ₆ , 60MHz): δ 6.23 (d,
1H), 6.40 (bs, 3H), 7.05 (d, 1H) IR (KBr): ν 3420, 3330, 3170, 2970,
2820, 1680, 1640, 1620, 1570 cm ^-1 UV λ ^MeOH _nax : 232, 258, 319 nm (2) Production of 4-chloro-2-n-octanoylaminopyrrolo[2,3-d]pyrimidine: Above (1) ) 2-Amino-4-chloropyrrolo[2,3-d]pyrimidine (16.9 g) was suspended and dissolved in dry pyridine (200 ml), and the mixture was stirred under ice cooling with n-octanoyl chloride (21.2 g). ) was added, the mixture was returned to room temperature and reacted for 1 hour. 9.9% ethanolic ammonia (w/v) was added to the reaction mixture, and the mixture was further stirred at room temperature for 2 hours, and then the solvent was distilled off under reduced pressure. Water (500 ml) was added to the residue, and the mixture was stirred at room temperature for 1 hour. The resulting insoluble matter was removed, washed with water in a tank and then with water, and dried to give yellow powder crystals (23.3 g).
This product was recrystallized from 1,2-dimethoxyethane to obtain the desired product (20.9 g). NMR ( _CDCl3 /DMSO- _d6 , 60MHz): δ
0.87 (t, 3H), 1.30 (bs, 10H), 2.50 (t, 2H),
6.43 (d, 1H), 7.30 (d, 1H), 10.37 (s, 1H),
12.10 (bs, 1H) IR (KBr): ν 3430, 3220, 2920, 1645,
1610, 1585, 1375 cm ^-1 Reference example 6 2-n-octanoylaminopyrrolo [2,3-
d] Production of pyrimidine-4-thione: 4-chloro-2-n-octanoylaminopyrrolo[2,3-d]pyrimidine (19.9 g) obtained in Reference Example 5 and thiourea (38 g) were - Suspend and dissolve in methoxyethanol (240ml) and heat at 100℃.
The reaction was stirred for 2.5 hours. After distilling off the solvent under reduced pressure,
1.8% heavy tank water (300 ml) was added to the residue, and the mixture was stirred well at room temperature. The resulting precipitate was collected and recrystallized from ethanol to obtain the desired product (15.7 g). NMR ( _CDCl3 /DMSO- _d6 , 60MHz): δ
0.87 (t, 3H), 1.33 (bs, 10H), 1.47 (t, 2H),
6.63 (q, 1H), 6.90 (q, 1H), 11.27 (bs, 2H),
13.20 (bs, 1H) IR (KBr): ν 3220, 1680, 1635, 1600,
1310cm ^-1 Reference Example 7 Production of 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidine-4-thione: 2-octanoylamino obtained in Reference Example 6 Pyrrolo[2,3-d]pyrimidine-4-thione (3.5g) and dibenzylamine (9.5g),
It was dissolved in water/acetic acid (1:4, 120 ml), 35% formalin (4.2 g) was added, and the mixture was reacted at 60°C for 14 hours. The solvent was distilled off under reduced pressure, water (30 ml) was added, and the mixture was distilled off again. 2N-HCl (64 ml) and methanol (100 ml) were added to the residue, and the mixture was stirred at 60°C for 1.5 hours. Most of the methanol was distilled off under reduced pressure, and the aqueous layer was made into an ammoniacal alkali. After adding acidic sodium sulfite (5.7 g), the mixture was extracted with chloroform. The chloroform layer was concentrated to dryness to obtain the crude target product (3.95 g). This product can be used directly in the next reaction without further purification. NMR (CDCl ₃ , 60MHz): δ 0.83 (t, 3H),
1.20 (bs, 10H), 2.70 (t, 2H), 4.07 (bs, 4H),
4.40 (bs, 2H), 7.20 (m, 11H) Reference example 8 5-N,N-diallylaminomethyl-2-n-
Production of octanoylaminopyrrolo[2,3-d]pyrimidin-4-one: In the same manner as in Reference Example 2, the desired product was prepared from 2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and diallylamine. I got something. Rf=0.12 (developing solvent, chloroform:methanol=7:1) Reference example 9 2-octanoylamino-5-(1-pyrrolidinyl)methylpyrrolo[2,3-d]pyrimidine-
Production of 4-one: In the same manner as in Reference Example 2, the desired product was obtained from 2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and pyrrolidine. Rf=0.24 (developing solvent, chloroform: 6.5%
NH ₃ /ethanol = 4:1) Reference example 10 (1) 2-benzoylaminopyrrolo [2,3-d]
Production of pyrimidin-4-one: In the same manner as in Reference Example 1, the desired product was obtained from 2-amipyrrolo[2,3-d]pyrimidin-4-one and benzoyl chloride. IR (KBr) 1635cm ^-1 (2) 5-N,N-dibenzylaminomethyl-2-
Production of benzoylaminopyrrolo[2,3-d]pyrimidin-4-one: In the same manner as in Reference Example 2, the desired product was prepared from 2-benzoylaminopyrrolo[2,3-d]pyrimidin-4-one and benzylamine. was gotten. Rf=0.35 (developing solvent, chloroform:methanol=4:1). Example 1 2-amino-5-[(3S,4R,5S)-4,5-dihydroxycyclopent-1-en-3-yl-
Production of aminomethyl]pyrrolo[2,3-d]pyrimidin-4-one (Q base): 2-amino-5-N,N- obtained in Reference Example 3
Dibenzylaminomethylpyrrolo[2,3-d]pyrimidin-4-one (359mg) and (3S,4R,5S)
-4,5-O-isopropylidene-4,5-dihydroxycyclopent-1-en-3-ylamine (310 mg) was dissolved in methanol and placed in a sealed tube for 60 min.
The reaction was carried out at ℃ for 24 hours. After adding an equal amount of 1N hydrochloric acid to this and heating it again at 70°C for 1 hour, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography using cellulose powder and ion exchange resin to obtain the desired product (65mg). )was gotten. Physical and chemical data is 5%
Measurements were made after conversion to the hydrochloride salt with w/w methanolic hydrochloric acid. NMR (D ₂ O, 60MHz) δ 4.28-4.60 (m,
2H), 4.50 (bs, 2H), 6.13 (dd, 1H), 6.35 (m,
1H), 7.12 (s, 1H). mp 230~235 (decomp.) IR (KBr): ν 3300, 3100, 2950, 2770,
1675, 1610cm ^-1 Example 2 2-Amino-5-aminomethylpyrrolo[2,3
-d] Production of pyrimidin-4-one (PreQ ₁ base): 2-amino-5-N,N- obtained in Reference Example 3
Dibenzylaminomethylpyrrolo[2,3-d]pyrimidin-4-one (320 mg) was dissolved in a mixture of 5% alcoholic ammonia (15 ml) and aqueous ammonia (15 ml) and heated in a sealed tube at 45°C for 17 hours. There was a warm reaction. After cooling, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography using cellulose powder and ion exchange resin to obtain the desired product (120 mg). Physical and chemical data were measured after converting to hydrochloride with methanolic hydrochloric acid. NMR (CD ₃ OD/D ₂ O, 60MHz) δ 4.32 (s,
2H), 7.12 (s, 1H) IR (KBr): ν 3100, 1670, 1605, 1050cm ^-1 mp 220-225℃ (decomp.) UV λ ^MeOH _nax 271, 260, 281nm Example 3 2-Amino-5 -aminomethylpyrrolo[2,3
-d] Production of pyrimidin-4-one (PreQ ₁ base): 5-N,N-dimethylaminomethyl-2-n-octanoylaminopyrrolo[2,3-d]pyrimidine- obtained in Reference Example 4 4-one (157 mg) in alcohol (25 ml) and 25% ammonia water (8 ml)
The solution was dissolved in a mixture of 100% and 100% of the total amount of 100% chloride, and reacted by heating at 75°C for 15 hours in a sealed tube. After cooling, a small amount of insoluble matter was removed and the liquid was concentrated to dryness to obtain a crude product. This product was purified by column chromatography using cellulose powder and ion exchange resin (Amberlite IRA-68, manufactured by Rohm and Haas, USA) to obtain the desired product (56 mg). The physical and chemical data were completely consistent with those obtained in Example 2. Example 4 2-amino-5-{(3S,4R,5S)-4,5-dihydroxycyclopent-1-en-3-ylaminomethyl}pyrrolo[2,3-d]pyrimidine-
Production of 4-thione (6-thioQ base): Crude 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidine-4-thione obtained in Reference Example 7 (3.3g)
and (3S,4R,5S)-4,5-O-isopropylidene-4,5-dihydroxycyclopent-1-en-3-ylamine (1.55 g) were dissolved in ethanol (150 ml) and placed in a sealed tube. The reaction was carried out at 75°C for 20 hours. After cooling, add tetrahydrofuran (75ml) to the reaction solution.
and 40% potassium hydroxide aqueous solution (11ml),
It was left at 5°C for 3 days. A 30% ammonium chloride aqueous solution (11 ml) was added to this, concentrated to dryness, and the residue was purified by silica gel column chromatography.
% _NH3 containing ethanol/chloroform (1:4)
When separated and purified using effluent solvent, 2-amino-5
-{(3S,4R,5S)-4,5-O-isopropylidene-4,5-dihydroxycyclopent-1-en-3-ylaminomethyl}pyrrolo[2,3-
d] Pyrimidine-4-thione was obtained. The entire amount of this was mixed with methanol (100 ml) and 2N-HCl (16
ml) and left overnight at room temperature, the solvent was concentrated to dryness to obtain the desired dihydrochloride (1.70 g). NMR (D ₂ O, 60MHz): δ 4.20-4.60 (m,
2H), 4.47 (bs, 2H), 6.13 (m, 2H), 7.03 (s,
1H) IR (KBr): ν 2930, 2780, 1690, 1590,
1200cm ^-1 Example 5 2-amino-5-aminomethylpyrrolo[2,3
-d]Pyrimidine-4-thione (6-thioPreQ ₁
Production of base): Crude 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidine-4-thione (1.0 g) obtained in Reference Example 7
ethanol (50ml), tetrahydrofuran (30ml)
ml) and concentrated aqueous ammonia (20 ml), and reacted in a sealed tube at 80°C for 1.5 hours. After distilling off the solvent under reduced pressure, the residue was washed with diethyl ether, and the insoluble matter was separated and purified using cellulose powder (Avicel, manufactured by Asahi Kasei Kogyo Co., Ltd.) using concentrated ammonia-saturated n-butanol as the eluent solvent to obtain the desired product (215 mg). )was gotten. Physical and chemical data were measured after converting to hydrochloride with methanolic hydrochloric acid. NMR (D ₂ O/CD ₃ OD・60MHz): δ 4.13 (bs,
2H), 6.90 (bs, 1H) IR (KBr): ν 2920, 1690, 1595, 1195 cm ^-1 Example 6 2-Amino-5-carboxymethylaminomethylpyrrolo[2,3-d]pyrimidin4-one Production: Crude 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (7.5 g) obtained in Reference Example 2 and glycine t-butyl ester ( 9.84g) and ethanol (225ml) and tetrahydrofuran (150ml).
The mixture was suspended in a mixed solution of and reacted with stirring at 70°C for 24 hours. The reaction solvent was distilled off under reduced pressure, and the residue was solidified by adding diethyl ether to obtain a light brown powder (5.5 g). This product was suspended in 8.9% ammonia ethyl alcohol (900 ml), stirred at room temperature for 6 days, the solvent was distilled off, and the product was purified by silica gel column chromatography to yield 2-amino-5-t-butoxycarbonylmethylaminopyrrolo[ 2,3-d]
Pyrimidin-4-one (2.83 g) was obtained. This material (1.62 g) was suspended in a mixture of methanol (55 ml) and tetrahydrofuran (55 ml), and after adding 1N caustic soda aqueous solution (55 ml), it was heated at room temperature.
The mixture was left stirring for 17 hours. Under ice cooling, adjust the pH with 1N hydrochloric acid.
When adjusted to 3.5, the desired product (1.31 g) was obtained as crystals. NMR (D ₂ O + DCl, 60MHz): δ 4.18 (s,
2H), 4.60 (s, 2H), 7.23 (s, 1H) IR (KBr): ν 3450, 3120, 1680, 1655,
1630, 1590, 1410, 1380, 1340, 1320, 835 cm ^-1 Example 7 2-amino-5-{N-(2,3-dihydroxypropyl)aminomethyl}pyrrolo[2,3-d]
Production of pyrimidin-4-one (dihydrochloride): 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (obtained in Reference Example 2) 7.28g)
and 3-amino-1,2-propanedil (6.83
g) was suspended in a mixture of ethanol (225 ml) and tetrahydrofuran (150 ml) and reacted with stirring at 70°C for 2 days. The reaction solution was concentrated to dryness, and the residue was mixed with methanol/tetrahydrofuran/diethyl ether (50%
ml/50ml/250ml) and solidified to obtain a white powder (3.54g). Suspend the entire amount in a mixture of methanol (100 ml) and tetrahydrofuran (100 ml), and add 25% w/w aqueous ammonia (200 ml).
After adding, the mixture was left at room temperature overnight. The solvent was distilled off, 0.5N hydrochloric acid (50ml) was added to the residue, and the mixture was concentrated to dryness again. The residue was recrystallized from methanol/diethyl ether to obtain the desired product (4.31 g). NMR (D ₂ O, 60MHz) δ: 3.28 (bd, 2H),
3.68 (bd, 2H), 4.43 (bs, 2H), 5.30 (m, 1H),
7.12 (bs, 1H) Example 8 2-amino-5-{N-2-(2-hydroxyethoxy)ethylaminomethyl}pyrrolo[2,3-
d] Production of pyrimidin-4-one (dihydrochloride): 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidine- 4-on (7.28
g) and 2-(2-aminoethoxy)ethanol to obtain the desired product (4.83 g). NMR ( _D2O , 60MHz) δ: 3.23 (bt, 3H), 3.50
~3.77 (m, 6H), 4.32 (s, 2H), 6.83 (bs, 1H) Example 9 Production of 5-allylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one : 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (7.28 g) obtained in Reference Example 2
and allylamine (4.28g) in ethanol (225ml)
suspended in a mixture of and tetrahydrofuran (150ml),
The reaction was carried out for 3 days at 60°C under nitrogen substitution. The reaction solution was heated to 0°C.
The desired product (3.43 g) was obtained as a white precipitate. IR (KBr) ν 3230, 3930, 2850, 1635,
1590, 1540, 1430, 1250, 1180, 920, 780 cm ^-1 Example 10 Production of 5-phenylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one: In Reference Example 2 The obtained 5-NN-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (7.4 g) and aniline (14 g) were mixed at a solubility ratio of ethanol to tetrahydrofuran of 7: 1 solvent (400ml) bath temperature 85
Stir at ℃ for 24.5 hours. The desired product (5 g) was obtained by cooling and collecting the precipitated crystals. IR (KBr) ν 3400, 3220, 2925, 1635 cm ^-1 Example 11 5-(p-chlorophenyl)aminomethyl-2
-Production of octanoylaminopyrrolo[2,3-d]pyrimidin-4-one: In the same manner as in Example 10, 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3 -d] The desired product was obtained from pyrimidin-4-one and p-chloroaniline. IR (KBr) ν 3410, 3220, 2925, 1635 cm ^-1 Example 12 5-(m-chlorophenyl)aminomethyl-2
-Production of octanoylaminopyrrolo[2,3-d]pyrimidin-4-one: In the same manner as in Example 10, 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3 -d] The desired product was obtained from pyrimidin-4-one and m-chloroaniline. IR (KBr) ν 3400, 3220, 2925, 1635 cm ^-1 Example 13 2-amino-5-(2-hydroxyphnylaminomethyl)pyrrolo[2,3-d]pyrimidine-4
Production of -one: 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (7.4 g) obtained in Reference Example 2 and orthoaminophenol ( (16.3 g) was stirred in a solvent (400 ml) with a volume ratio of ethanol to tetrahydrofuran of 2:1 at a bath temperature of 80° C. for 65 hours. The solvent was distilled off under reduced pressure, 1000 ml of ethyl acetate was added to the residue, and the mixture was thoroughly stirred to remove the insoluble matter. This was stirred at room temperature for 40 hours in a solvent (200 ml) with a volume ratio of methanol to tetrahydrofuran of 1:1 and 25% w/w aqueous ammonia (150 ml). The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the desired product (2.1 g). NMR (CF ₃ COOH−D ₂ O, 60MHz) δ: 4.37
(bs, 2H), 6.37~7.10 (m, 5H) IR (KBr) ν 3460, 3160, 1675, 1655, 1610
cm ^-1 Example 14 Preparation of 2-amino-5-benzylaminomethylpyrrolo[2,3-d]pyrimidin-4-one: In the same manner as in Example 13, 5-N,N-dibenzylaminomethyl The desired product was obtained from -2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and benzylamine. NMR (DMSO-d ₆ , 60MHz) δ: 4.20 (bs,
4H), 6.70 (bs, 2H), 6.73 (bs, 1H), 7.40 (bs,
5H), 8.43 (bs, 2H), 11.33 (bs, 1H) IR (KBr) ν 3130, 1660, 1645, 1605, 1395
cm ^-1 Example 15 Production of 5-(2-adamantylaminomethyl)-2-aminopyrrolo[2,3-d]pyrimidin-4-one (dihydrochloride): 5-N obtained in Reference Example 2, N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (7.4g),
2-adamantanamine hydrochloride (10.5g), 28%
A w/w sodium methylate methanol solution (5.8 g) and potassium acetate (2.25 g) were stirred in ethanol (500 ml) at a bath temperature of 80° C. for 40 hours. The solvent was distilled off under reduced pressure, and the residue was mixed with a solvent (400
ml) to remove insoluble matter, and washed with water (150 ml). This was dissolved in a mixture of methanol (150 ml) and 2N hydrochloric acid (30 ml), and the newly precipitated crystals were removed to obtain the desired product (3.5 g). NMR (CF ₃ CO ₂ H−D ₂ O, 60MHz) δ: 2.00−
2.23 (bm, 14H), 3.60 (bs, 1H), 4.43 (bs, 2H),
7.07 (s, 1H) IR (KBr) ν 3200, 2925, 1705, 1690 cm ^-1 Example 16 2-Amino-5-cyclopentylaminomethylpyrrolo[2,3-d]pyrimidin-4-one (2
Hydrochloride) Production: 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one (2.9 g) obtained in Reference Example 2 and cyclopentylamine ( (5.1 g) was stirred for 22 hours at a bath temperature of 90° C. in a solvent (200 ml) with a volume ratio of ethanol to tetrahydrofuran of 1:1. The solvent was distilled off under reduced pressure and the residue was dissolved in a solvent (120 ml) with a volume ratio of ethanol to tetrahydrofuran of 1:1.
Dissolve in 5NKOH (8.4ml) and heat at 5℃ for 6 hours.
It was left undisturbed for a day. Ammonium chloride (2.4 g) was added and distilled off, and tetrahydrofuran was added to the residue, stirred well to remove insoluble matter, stirred well with water (100 ml), and then collected again. Add this to 1N hydrochloric acid (20
ml) and dried under reduced pressure to obtain the desired product (1.6 g).
was gotten. NMR (D ₂ O, 60MHz) δ: 1.67-2.40 (m,
8H), 3.67 (m, 1H), 4.30 (s, 2H), 7.00 (s,
1H) IR (KBr) ν 3200, 3100~2400, 1680, 1600
cm ^-1 Example 17 Preparation of 2-amino-5-n-hexylaminomethylpyrrolo[2,3-d]pyrimidin-4-one (dihydrochloride): Same method as Example 16, 5-N, The desired product was obtained from N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and n-hexylamine. NMR (D ₂ O, 60MHz) δ: 0.87 (t, 3H), 1.07
~2.03 (bm, 8H), 3.12 (t, 2H), 4.32 (s,
2H), 7.00 (s, 1H) IR (KBr) ν 3300, 2960, 2930, 2770,
2720, 2430, 1700, 1675, 1620, 1580, 1440,
1380, 1245, 1100, 1050, 810 cm ^-1 Example 18 Production of 2-amino-5-isoamylaminomethylpyrrolo[2,3-d]pyrimidin-4-one (dihydrochloride): Same as Example 16 By this method, the desired product was obtained from 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and ylamylamine. NMR (D ₂ O, 60MHz) δ: 0.96 (d, 3H), 1.00
(d, 3H), 1.20-2.16 (m, 3H), 2.93-3.18 (m,
2H), 4.36 (s, 2H), 7.06 (s, 1H) IR (KBr) ν 3280, 3180, 2970, 2720,
1695, 1680, 1620, 1580, 1450, 1420, 1380,
1240, 1130, 1100, 1050, 820 cm ^-1 Example 19 2-amino-5-piperidinomethylpyrrolo[2,3-d]pyrimidin-4-one (dihydrochloride)
Production: In the same manner as in Example 16, the desired product was obtained from 5-N,N-dibenzylaminomethyl-2-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and piperidine. Ta. NMR (CD ₃ OD/D ₂ O, 60MHz) δ: 1.80 (m,
6H), 2.80-3.67 (m, 4H), 1.30 (q, 2H), 7.02
(s, 1H) IR (KBr) ν 3370, 3175-2500, 1680 cm ^-1 Example 20 2-amino-5-[(3S,4R,5S)-4,5-dihydroxycyclopent-1-ene-3 -il-
Production of aminomethyl]pyrrolo[2,3-d]pyrimidin-4-one- (Q base): 5-N,N-diallylaminomethyl- obtained in Reference Example 8 in the same manner as in Example 1. 2-n-octanoylaminopyrrolo[2,3-d]pyrimidin-4-one and (3S,4R,5S)-4,5-O-isopropylidene-4,5-dihydroxycyclopent-1-ene- The desired product was obtained from 3-ylamine. The physical and chemical data were completely consistent with those obtained in Example 1. Example 21 2-amino-5-aminomethylpyrrolo[2,3
-d] Production of pyrimidin-4-one (PreQ ₁ base): 2-octanoylamino-5-(1-pyrrolidinyl)methylpyrrolo[2,3 -d]pyrimidine-4
The desired product was obtained from -one and aqueous ammonia. The physical and chemical data were completely consistent with those obtained in Example 2. Example 22 2-amino-5-aminomethylpyrrolo[2,3
-d] Production of pyrimidin-4-one (PreQ ₁ base): 5-N,N-dibenzylaminomethyl-2-benzoylaminopyrrolo[2] obtained in Reference Example 10 in the same manner as in Example 3. ,3-d]pyrimidine-
The desired product was obtained from 4-one and aqueous ammonia. The physical and chemical data were completely consistent with those obtained in Example 2.

Claims (1)

[Claims] 1. General formula [In the formula, R ₁ represents a hydrogen atom, an alkanoyl group, or an aroyl group, R ₂ and R ₃ represent an alkyl group, an alkenyl group, or an aralkyl group with a methylene group at the α position, and R ₂ and R ₃ are adjacent to each other. may form a cyclic amino group together with the nitrogen atom. ] The 7-deazapurine derivative or its salt represented by the general formula [In the formula, R ₄ and R ₅ each represent a hydrogen atom or an alkyl group, an alkenyl group, a cycloalkyl group, a cycloalkenyl group, an aralkyl group, or an aryl group, each of which may have a substituent, and R ₄
and R ₅ may form a cyclic amino group together with the adjacent nitrogen atom. However, the [Formula] group is not the same as the [Formula] group. ] A general formula characterized by being subjected to a substitution reaction with an amine represented by or a salt thereof [In the formula, R ₁ , R ₄ and R ₅ have the same meanings as above. ] A method for producing a 7-deazapurine derivative or a salt thereof.